Genomewide Analysis of PRC1 and PRC2 Occupancy Identifies Two Classes of Bivalent Domains

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Genomewide Analysis of PRC1 and PRC2 Occupancy Identifies Two Classes of Bivalent Domains

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dc.contributor.author Rheinbay, Esther
dc.contributor.author Endoh, Mitsuhiro
dc.contributor.author Mikkelsen, Tarjei S.
dc.contributor.author Nusbaum, Chad
dc.contributor.author Xie, Xiaohui
dc.contributor.author Adli, Mazhar
dc.contributor.author Kasif, Simon
dc.contributor.author Ptaszek, Leon M.
dc.contributor.author Koseki, Haruhiko
dc.contributor.author van Steensel, Bas
dc.contributor.author Ku, Manching
dc.contributor.author Koche, Richard Patrick
dc.contributor.author Mendenhall, Eric M
dc.contributor.author Presser, Aviva
dc.contributor.author Chi, Andrew S.
dc.contributor.author Cowan, Chad A.
dc.contributor.author Lander, Eric Steven
dc.contributor.author Bernstein, Bradley E.
dc.date.accessioned 2010-09-30T17:24:21Z
dc.date.issued 2008
dc.identifier.citation Ku, Manching, Richard P. Koche, Esther Rheinbay, Eric M. Mendenhall, Mitsuhiro Endoh, Tarjei S. Mikkelsen, Aviva Presser, et al. 2008. Genomewide analysis of PRC1 and PRC2 occupancy identifies two classes of bivalent domains. PLoS Genetics 4(10): e1000242. en_US
dc.identifier.issn 1553-7390 en_US
dc.identifier.uri http://nrs.harvard.edu/urn-3:HUL.InstRepos:4454678
dc.description.abstract In embryonic stem (ES) cells, bivalent chromatin domains with overlapping repressive (H3 lysine 27 tri-methylation) and activating (H3 lysine 4 tri-methylation) histone modifications mark the promoters of more than 2,000 genes. To gain insight into the structure and function of bivalent domains, we mapped key histone modifications and subunits of Polycomb-repressive complexes 1 and 2 (PRC1 and PRC2) genomewide in human and mouse ES cells by chromatin immunoprecipitation, followed by ultra high-throughput sequencing. We find that bivalent domains can be segregated into two classes—the first occupied by both PRC2 and PRC1 (PRC1-positive) and the second specifically bound by PRC2 (PRC2-only). PRC1-positive bivalent domains appear functionally distinct as they more efficiently retain lysine 27 tri-methylation upon differentiation, show stringent conservation of chromatin state, and associate with an overwhelming number of developmental regulator gene promoters. We also used computational genomics to search for sequence determinants of Polycomb binding. This analysis revealed that the genomewide locations of PRC2 and PRC1 can be largely predicted from the locations, sizes, and underlying motif contents of CpG islands. We propose that large CpG islands depleted of activating motifs confer epigenetic memory by recruiting the full repertoire of Polycomb complexes in pluripotent cells. en_US
dc.description.sponsorship Stem Cell and Regenerative Biology en_US
dc.language.iso en_US en_US
dc.publisher Public Library of Science en_US
dc.relation.isversionof doi:10.1371/journal.pgen.1000242 en_US
dc.relation.hasversion http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2567431/pdf/ en_US
dash.license OAP
dc.subject developmental biology en_US
dc.subject developmental molecular mechanisms en_US
dc.subject stem cells en_US
dc.subject genetics and genomics en_US
dc.subject bioinformatics en_US
dc.subject epigenetics en_US
dc.subject functional genomics en_US
dc.subject molecular biology en_US
dc.subject histone modification en_US
dc.title Genomewide Analysis of PRC1 and PRC2 Occupancy Identifies Two Classes of Bivalent Domains en_US
dc.type Journal Article en_US
dc.description.version Version of Record en_US
dc.relation.journal PLoS Genetics en_US
dash.depositing.author Cowan, Chad A.
dc.date.available 2010-09-30T17:24:21Z

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  • FAS Scholarly Articles [6463]
    Peer reviewed scholarly articles from the Faculty of Arts and Sciences of Harvard University

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